Cyclobutanone → 1-[2-[[Tert-butyl(dimethyl)silyl]oxymethyl]-6-(methoxymethoxy)-3-methyl-phenyl]cyclobutanol

HRID 527636Notes

Reaction equation

HRID 527636 reaction equation
[C:1]([Si:5]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH2:17][O:18][CH3:19])[CH:13]=[CH:12][C:11]=1[CH3:20])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[C:21]1(=[O:25])[CH2:24][CH2:23][CH2:22]1>CCCCCC.[Li]CCCC.C1COCC1>[Si:5]([O:8][CH2:9][C:10]1[C:11]([CH3:20])=[CH:12][CH:13]=[C:14]([O:16][CH2:17][O:18][CH3:19])[C:15]=1[C:21]1([OH:25])[CH2:24][CH2:23][CH2:22]1)([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:7])[CH3:6]

Participants

6

Reactant 2

HCID 14496CyclobutanoneHCID 67958358Tert-butyl-[[5-(methoxymethoxy)-2-methyl-phenyl]methoxy]-dimethyl-silane2×

Product 1

HCID 679582151-[2-[[Tert-butyl(dimethyl)silyl]oxymethyl]-6-(methoxymethoxy)-3-methyl-phenyl]cyclobutanolYield 13.7%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 178418339ButyllithiumSolvent

Procedure

To a solution of tert-butyl-[[5-(methoxymethoxy)-2-methyl-phenyl]methoxy]-dimethyl-silane (Intermediate 174, 0.3 g, 1 mmol) in hexane (5 ml), BuLi (1.6M in hexane, 0.9 ml, 1.4 mmoli) was added at room temperature. The reaction mixture was stirred for 2 h and then added dropwise at −30° C. to a suspension of CeCl3 (0.37 g, 1.5 mmoli) in dry THF (5 ml) that was previously stirred at room temperature overnight. After 45 min at −30° C., cyclobutanone (0.07 g, 1 mmoli) dissolved in THF (1 ml) was added. The reaction was stirred at the same temperature for and then quenched with ammonium chloride (20 ml) and extracted with Ethyl Acetate (2×20 ml). Combined organic layers were dried over Na2SO4 and evaporated under vacuum to afford a colorless oil that was purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 75:25 as eluents affording the title compound (0.05 g) as a colorless oil.

Workup

  1. stirringwas previously stirred at room temperature overnight
  2. waitAfter 45 min at −30° C.
  3. additionwas added
  4. stirringThe reaction was stirred at the same temperature for and
  5. customthen quenched with ammonium chloride (20 ml)
  6. extractionextracted with Ethyl Acetate (2×20 ml)
  7. dry with materialCombined organic layers were dried over Na2SO4
  8. customevaporated under vacuum
  9. customto afford a colorless oil that
  10. customwas purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 75:25 as eluents

Sources & evidence

ORD record
ord-09ed5e16336748ff9b24fd584a55a6e4
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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